Abstract

Background

Neurons in the capsular part of the central nucleus of the amygdala (CeC), a region
also called "nociceptive amygdala," receive nociceptive information from the dorsal
horn via afferent pathways relayed from the lateral parabrachial nucleus (LPB). As
the central amygdala is known to be involved in the acquisition and expression of
emotion, this pathway is thought to play central roles in the generation of affective
responses to nociceptive inputs. Excitatory synaptic transmission between afferents
arising from the LPB and these CeC neurons is potentiated in arthritic, visceral,
neuropathic, inflammatory and muscle pain models. In neuropathic pain models following
spinal nerve ligation (SNL), in which we previously showed a robust LPB-CeC potentiation,
the principal behavioral symptom is tactile allodynia triggered by non-C-fiber low-threshold
mechanoreceptor afferents. Conversely, recent anatomical studies have revealed that
most of the spinal neurons projecting to the LPB receive C-fiber afferent inputs.
Here, we examined the hypothesis that these C-fiber-mediated inputs are necessary
for the full establishment of robust synaptic potentiation of LPB-CeC transmission
in the rats with neuropathic pain.

Results

Postnatal capsaicin treatment, which has been shown to denervate the C-fibers expressing
transient receptor potential vanilloid type-1 (TRPV1) channels, completely abolished
eye-wiping responses to capsaicin eye instillation in rats, but this treatment did
not affect mechanical allodynia in the nerve-ligated animals. However, the postnatal
capsaicin treatment prevented LPB-CeC synaptic potentiation after SNL, unlike in the
vehicle-treated rats, primarily due to the decreased incidence of potentiated transmission
by elimination of TRPV1-expressing C-fiber afferents.

Conclusions

C-fiber-mediated afferents in the nerve-ligated animals may be a required facilitator
of the establishment of nerve injury-evoked synaptic potentiation in the CeC. These
inputs might play essential roles in the chronic pain-induced plastic changes in the
central network linking nociception and negative emotion.